Patient Education Blog

Archive for the ‘Inherited (genetic)’ Category

Antiphospholipid Syndrome: Can the New Oral Blood Thinners Be Used?

| Anticoagulants, Antiphospholipid antibodies, Deep vein thrombosis (DVT), Edoxaban, Eliquis, Eliquis - Apixaban, Pradaxa - dabigatran, Pulmonary embolism, Savaysa - Edoxaban, Venous clots, Xarelto - Rivaroxaban | Comments Off on Antiphospholipid Syndrome: Can the New Oral Blood Thinners Be Used?

Stephan Moll, MD and Damon Houghton, MD write … Antiphospholipid syndrome (APS) is an acquired clotting disorder.  Patients with APS may have DVT or PE that requires treatment with blood thinners. Warfarin (Coumadin®, Jantoven®), and sometimes the injectable heparin drugs (enoxaparin = Lovenox®; dalteparin = Fragmin®; tinzaparin = Innohep®; etc.), have traditionally been used in patients with APS.  A question that comes up is whether one of the new oral blood thinners (apixaban = Eliquis®; dabigatran = Pradaxa®; edoxaban = Savaysa®; rivaroxaban = Xarelto®) can be used instead of warfarin or a heparin drug.  These drugs are collectively referred to as direct oral anticoagulants (DOACs).

It is not known at this point whether DOACs are equally, more or less effective as/than warfarin in patients with APS.  Data from clinical trials directly comparing DOACs with warfarin are not yet available.  Given the absence of data, no formal recommendations or guidelines exist on this topic.  It is an individualized decision between a physician and patient with APS whether to use warfarin or a DOAC for the treatment of DVT or PE.

Published Data

Multiple cases of patients with APS treated with a DOAC have been published. All of these (i.e. a total of 122 patients) have recently been summarized [ref 1]: Sixteen percent (i.e. one of every 6 patients) had a recurrent clot on a DOAC.  As this is a high rate of DOAC failure, the authors caution about the use of DOACs in APS.  However, two things need to be considered: (a) it is also known that warfarin has a high failure rate [references 2,3]; and (b) due to the nature of case report publications (potential bias; absence of control group), no strong or meaningful conclusion is really possible as to how DOACs compare to warfarin in the treatment of DVT and PE in patients with APS

Ongoing Studies

Several studies on APS and the use of DOACs are ongoing.  Details of the following studies can be found at clinicaltrials.gov:

  1. NCT02157272: A Prospective, Randomized Clinical Trial Comparing Rivaroxaban with Warfarin in High Risk Patients With Antiphospholipid Syndrome (TRAPS)
  2. NCT02295475: Apixaban for the Secondary Prevention of Thromboembolism Among Patients With the AntiphosPholipid Syndrome (ASTRO-APS)
  3. NCT02116036: Rivaroxaban for Antiphospholipid Antibody Syndrome (RAPS)

Our practice

This is what we discuss with the patient with APS who needs to be on a blood thinner:

  1. I highlight that no solid data exist regarding the use of DOACs in APS, and that it is not known whether the DOACs are as effective as warfarin, less effective or more effective.
  2. I discuss the fact that some patients with APS develop new clots in spite of being on warfarin and that recurrent clots may also occur on a DOAC.

If we decide to use a DOAC, then our preference is typically to use a twice daily dosed blood thinner (Eliquis® or Pradaxa®) rather than a once daily dosed drug (Xarelto® or Savaysa®).  The thought behind this is that a twice daily dosed drug leads to more steady drug levels throughout the day and that this may lead to a more effective blood thinning effect.  However, this is a theory unproven, and whether this truly leads to a lower risk of recurrent clots than being on a once daily drug is not known.  A recent publication of a case report with discussion of drug metabolism also favors a twice daily rather than a once daily dosed drug in patients with APS [ref 4].  Ultimately, the most effective medication is likely the one that is taken as prescribed; therefore, a patient’s preference regarding the feasibility and practicality of a once daily versus twice daily medication is also an important consideration.

References

  1. Dufrost V et al. Direct oral anticoagulants use in antiphospholipid syndrome: Are these drugs an effective and safe alternative to warfarin? A systematic review of the literature. Curr Rheumatol Rep 2016;18:74.
  2. Crowther M et al. A Comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 2003;349:1133-8.
  3. Finazzi G et al. A randomized clinical trial of high-intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome (WAPS) J Thromb Haemost 2005;3: 848–853.
  4. Schofield JR et al. Dosing considerations in the use of the direct oral anticoagulants in the antiphospholipid syndrome. J Clin Pharm Ther. 2017 Jun 27. doi: 10.1111/jcpt.12582. [Epub ahead of print].

 

Disclosure: Dr. Moll has consulted for Janssen Pharmaceuticals and Boehringer-Ingelheim. Dr. Houghton has no disclosures.

Last updated: July 5th, 2017

Clotting Disorders (Thrombophilia): Who Should Be Tested? What To Test?

| Antiphospholipid antibodies, Antithrombin deficiency, APC resistance, Clotting disorder - thrombophilia, Factor V Leiden, Homocysteine, MTHFR, Inherited (genetic), Protein C deficiency, Protein S deficiency, Prothrombin 20210 mutation, Thrombophilia lab tests, Whom to test | Comments Off on Clotting Disorders (Thrombophilia): Who Should Be Tested? What To Test?

Stephan Moll, MD writes… A publication today in the journal Vascular Medicine discusses – for patients and family members – (a) in which patient with blood clots (DVT, PE) to consider testing for a clotting disorder, (b) what tests might be appropriate to do, (c) how the test results influence management with blood thinners, (d) what birth control methods are safe in women with history of blood clots or a clotting disorder,  and (e) in which family members to consider thrombophilia testing (link here for the article).

 

Disclosures:  None

Last updated: April 1st, 2015

 

 

Testing for Clotting Disorders – Can It Be Done While on Blood Thinners?

| Acquired risk factors, Antiphospholipid antibodies, Antithrombin deficiency, APC resistance, Clotting disorder - thrombophilia, Factor V Leiden, Inherited (genetic), Protein C deficiency, Protein S deficiency, Prothrombin 20210 mutation | Comments Off on Testing for Clotting Disorders – Can It Be Done While on Blood Thinners?

Stephan Moll, MD writes…  The decision how long to treat a patient who has had a DVT or PE with blood thinners can often be made based just on the patient’s history. Often no testing for clotting disorders (thrombophilias) is needed.  The decision how long to treat is influenced by 3 factors: (1) What is the person’s risk of another clot if he/she is not on blood thinners any more? (2) What is the person’s risk for bleeding on blood thinners? (3) What is the person’s own preference regarding his/her treatment. These issues are discussed in detail here.

However, if one were to do testing, what is the  right time to test? It is important to know that some blood thinners can influence test results.

Read the rest of this entry »

Thrombophilia and Insurance

| Clotting disorder - thrombophilia, Inherited (genetic), Psychological and social consequences of blood clots, Thrombophilia lab tests | 4 Comments »

Liz Varga, Certified Genetic Counselor, Nationwide Children’s Hospital, Columbus OH writes….

Some people may have concerns about genetic testing for clotting disorders (thrombophilias) for fear of genetic discrimination.  Fortunately in the United States, we have laws in place that can alleviate this concern. Read the rest of this entry »

Protein C Deficiency

| Inherited (genetic), Protein C deficiency | 2 Comments »

What is Protein C?

Protein C is a protein in our blood stream, which prevents blood from clotting too much.  It’s a sort of police protein that keeps our clotting in check.  If protein C levels are low, a person will have a tendency to clot more easily.  Elevated levels of protein C, on the other hand, appear to be irrelevant; they do not lead to an increased bleeding tendency.

What Problems Does Protein C Deficiency Cause?
Inherited protein C deficiency increases the risk for blood clots;  Read the rest of this entry »

Pregnancy Loss and Clotting Disorders

| Antiphospholipid antibodies, Antithrombin deficiency, Clotting disorder - thrombophilia, Factor V Leiden, Protein C deficiency, Protein S deficiency, Prothrombin 20210 mutation, Therapy, Women and blood clots | 8 Comments »

How common is pregnancy loss? What are the causes?

Pregnancy loss (= miscarriage) in the general population is common. Most losses occur in the first trimester. As many as 5 % of women have 2 or more early losses; 1-2 % have 3 or more early losses [ref 1]. Well established risk factors for pregnancy loss are: (a) advanced age of the mother, (b) anatomic abnormalities of the uterus (such as fibroids), (c) chromosome abnormalities of fetus, the mother or the father, (d) underlying diseases of the mother (endocrine, immunologic), (e) maternal hormonal unbalances.  The acquired clotting disorder called “antiphospholipid antibody syndrome” is also a risk factor for pregnancy loss. The role of inherited clotting disorders (= thrombophilias) contributing to pregnancy loss is less clear. Read the rest of this entry »

Family Member Testing for Thrombophilia

| Clotting disorder - thrombophilia, Factor V Leiden, Inherited (genetic), Protein C deficiency, Protein S deficiency, Prothrombin 20210 mutation, Thrombophilia lab tests | 4 Comments »

Stephan Moll, MD writes…

Background

If a thrombophilia (clotting disorder) has been identified in a patient with blood clots (venous thromboembolism = VTE), the question arises whether other family members should be tested for the same thrombophilia.

My Clinical Approach

My approach in clinical practice to thrombophilia testing in family members is summarized in table 1:  Testing of Family Members. Read the rest of this entry »